Bottom Line:
The study reveals that energy consumption increases in telomere dysfunctional cells resulting in enhanced glucose metabolism both in glycolysis and in the tricarboxylic acid cycle at organismal level.The beneficial effects of glucose substitution on mitochondrial function and glucose metabolism are blocked by mTOR inhibition but mimicked by IGF-1 application.Together, these results provide the first experimental evidence that telomere dysfunction enhances the requirement of glucose substitution for the maintenance of energy homeostasis and IGF-1/mTOR-dependent mitochondrial biogenesis in ageing tissues.

Mentions:
Previous studies revealed that telomere dysfunction leads to impairments in mitochondrial biogenesis and function by activating p53/p21-dependent signalling67. In agreement with these studies, 12- to 15-month-old G3 mTerc−/− mice that lost body weight on normal diet exhibited impaired mitochondrial biogenesis in various tissues (such as liver, skeletal muscle and haematopoietic cells) as indicated by reduction in mitochondrial DNA (mtDNA) copy number (Fig. 5a and Supplementary Fig. 2B) and reduced expression of transcriptional regulators of mitochondrial biogenesis (Fig. 5b). In line with reductions in mtDNA, the expression of mitochondrial enzymes (cytochrome c oxidase and citrate synthase) were reduced in liver lysates of 12- to 15-month-old G3 mTerc−/− mice with weight loss on normal diet compared with mTerc+/+ mice (Fig. 5c,d).

Bottom Line:
The study reveals that energy consumption increases in telomere dysfunctional cells resulting in enhanced glucose metabolism both in glycolysis and in the tricarboxylic acid cycle at organismal level.The beneficial effects of glucose substitution on mitochondrial function and glucose metabolism are blocked by mTOR inhibition but mimicked by IGF-1 application.Together, these results provide the first experimental evidence that telomere dysfunction enhances the requirement of glucose substitution for the maintenance of energy homeostasis and IGF-1/mTOR-dependent mitochondrial biogenesis in ageing tissues.